Details of the Drug

General Information of Drug (ID: DMWH7NQ)

• Drug Name: Alprostadil
• Synonyms: Prostaglandin E1; alprostadil; 745-65-3; PGE1; Muse; Edex; Caverject; Prostin VR; Alprostadilum; Femprox; Befar; Vitaros; Prostandin; Liprostin; PGE-1; Prink (TN); Befar (TN); Prostavasin; Vasaprostan; MR-256; Minprog; UNII-F5TD010360; Alprostadil(Caverject); CHEMBL495; (11alpha,13E,15S)-11,15-dihydroxy-9-oxoprost-13-en-1-oic acid; Prostivas; Lipoprost; 11alpha,15alpha-Dihydroxy-9-oxo-13-trans-prostenoic acid; (13E)-(15S)-11alpha,15-Dihydroxy-9-oxoprost-13-enoate; FemLife; RayVa; Sugiran; Viridal; MR 256; PGE1 Oligomer; BML1-F06; Caverject (TN); Edex (TN); HEI-507; Muse (TN); Prostin VR pediatric (TN); U-10136; Alprostadil (JP15/USP/INN); Prost-13-en-1-oic acid, 11,15-dihydroxy-9-oxo-, (11alpha,13E,15S)-, homopolymer; (11alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-enoic acid; (13E,15S)-11alpha,15-dihydroxy-9-oxoprost-13-en-1-oic acid; 7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]heptanoic acid; Lipo-alprostadil

Indication

Disease Entry	ICD 11	Status	REF
Aorta coarctation	N.A.	Approved	[1]
Diabetic foot ulcer	BD54	Approved	[2]
Erectile dysfunction	HA01.1	Approved	[3]
Pulmonary hypertension	BB01	Approved	[1]
Tetralogy of fallot	N.A.	Approved	[1]

• Therapeutic Class: Vasodilator Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 354.5
  Logarithm of the Partition Coefficient (xlogp); 3.2
  Rotatable Bond Count (rotbonds); 13
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 45.4 mL/min/kg [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 10 minutes [4]
  Metabolism: The drug is metabolized via the lung []
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 2.4 L/kg [4]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Miosis	Not Available	AVPR1A	OTKR8AFL	[5]

• Chemical Identifiers:
  Formula: C20H34O5
  IUPAC Name: 7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]heptanoic acid
  Canonical SMILES: CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1CCCCCCC(=O)O)O)O
  InChI: InChI=1S/C20H34O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h12-13,15-17,19,21,23H,2-11,14H2,1H3,(H,24,25)/b13-12+/t15-,16+,17+,19+/m0/s1
  InChIKey: GMVPRGQOIOIIMI-DWKJAMRDSA-N
• Cross-matching ID:
  PubChem CID: 5280723
  ChEBI ID: CHEBI:15544
  CAS Number: 745-65-3
  DrugBank ID: DB00770
  TTD ID: D0I4DQ
  VARIDT ID: DR00210
  INTEDE ID: DR1923
  ACDINA ID: D00828
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin E2 receptor EP2 (PTGER2)	TT1ZAVI	PE2R2_HUMAN	Agonist	[2]
Thromboxane A2 receptor (TBXA2R)	TT2O84V	TA2R_HUMAN	Modulator	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 2A1 (SLCO2A1)	DT021JD	SO2A1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 3A1 (SLCO3A1)	DTVNRXW	SO3A1_HUMAN	Substrate	[8]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[9]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[10]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Prostaglandin dehydrogenase 1 (HPGD) Main DME	DEHKSC6	PGDH_HUMAN	Substrate	[11]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Gene/Protein Processing	[12]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Post-Translational Modifications	[13]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Gene/Protein Processing	[14]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Gene/Protein Processing	[15]
Prostaglandin D2 receptor (PTGDR)	OT92UR1A	PD2R_HUMAN	Protein Interaction/Cellular Processes	[16]
Renin (REN)	OT52GZR2	RENI_HUMAN	Gene/Protein Processing	[12]
Vasodilator-stimulated phosphoprotein	OTFC3010	VASP_HUMAN	Post-Translational Modifications	[17]
Vasopressin V1a receptor (AVPR1A)	OTKR8AFL	V1AR_HUMAN	Drug Response	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Aorta coarctation

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin E2 receptor EP2 (PTGER2)	DTT	PTGER2	2.77E-06	1.15	1.37
Organic anion transporting polypeptide 3A1 (SLCO3A1)	DTP	OATP3A1	9.66E-01	2.27E-01	3.78E-01
Organic anion transporter 1 (SLC22A6)	DTP	OAT1	7.57E-01	6.84E-02	1.89E-01
Multidrug resistance-associated protein 4 (ABCC4)	DTP	MRP4	3.78E-01	-2.23E-02	-1.90E-02
Organic anion transporting polypeptide 2A1 (SLCO2A1)	DTP	OATP2A1	6.15E-01	-3.02E-02	-2.83E-02
Prostaglandin dehydrogenase 1 (HPGD)	DME	HPGD	8.89E-04	-1.60E+00	-7.87E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alprostadil (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ardeparin	DMYRX8B	Moderate	Increased risk of bleeding by the combination of Alprostadil and Ardeparin.	Coronary thrombosis [BA43]	[18]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Benzyl alcohol	E00010	244	Antimicrobial preservative; Solvent
Hydrochloric acid	E00015	313	Acidulant
Sodium citrate anhydrous	E00102	6224	Alkalizing agent; Buffering agent; Complexing agent; Emulsifying agent
Alfadex	E00419	444913	Other agent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Sodium hydroxide	E00234	14798	Alkalizing agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Alprostadil 0.01mg/vial injectable	0.01mg/vial	Injectable	Injection
Alprostadil 0.005mg/vial injectable	0.005mg/vial	Injectable	Injection

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Alprostadil FDA Label
• [2] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1882).
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [6] Flow after prostaglandin E1 is mediated by receptor-coupled adenylyl cyclase in human anterior segments. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2622-6.
• [7] Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9.
• [8] Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97.
• [9] The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
• [10] Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3. Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7.
• [11] Effect of calcium ionophore A23187 on prostaglandin synthase type 2 and 15-hydroxy-prostaglandin dehydrogenase expression in human chorion trophoblast cells. Am J Obstet Gynecol. 2008 Nov;199(5):554.e1-8.
• [12] Catecholamine and renin-angiotensin response during controlled hypotension induced by prostaglandin E1 combined with hemodilution during isoflurane anesthesia. J Clin Anesth. 1997 Jun;9(4):321-7. doi: 10.1016/s0952-8180(97)00011-1.
• [13] Characterization of agonist stimulation of cAMP-dependent protein kinase and G protein-coupled receptor kinase phosphorylation of the beta2-adrenergic receptor using phosphoserine-specific antibodies. Mol Pharmacol. 2004 Jan;65(1):196-206. doi: 10.1124/mol.65.1.196.
• [14] Effects of prostaglandin E1, dobutamine and placebo on hemodynamic, renal and neurohumoral variables in patients with advanced heart failure. Jpn Heart J. 1999 May;40(3):321-34. doi: 10.1536/jhj.40.321.
• [15] Short-term effects of levosimendan and prostaglandin E1 on hemodynamic parameters and B-type natriuretic peptide levels in patients with decompensated chronic heart failure. Eur J Heart Fail. 2005 Dec;7(7):1156-63. doi: 10.1016/j.ejheart.2005.05.001. Epub 2005 Aug 5.
• [16] Characterization of the recombinant human prostanoid DP receptor and identification of L-644,698, a novel selective DP agonist. Br J Pharmacol. 1998 Apr;123(7):1317-24.
• [17] Arsenic trioxide-mediated antiplatelet activity: pivotal role of the phospholipase C gamma 2-protein kinase C-p38 MAPK cascade. Transl Res. 2010 Feb;155(2):97-108. doi: 10.1016/j.trsl.2009.08.005. Epub 2009 Sep 15.
• [18] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".